Epitope-dependent effect of long-term cART on maintenance and recovery of HIV-1-specific CD8+ T cells

J Virol. 2023 Nov 30;97(11):e0102423. doi: 10.1128/jvi.01024-23. Epub 2023 Oct 25.

Abstract

HIV-1-specific CD8+ T cells are anticipated to become effector cells for curative treatment using the "shock and kill" approach in people living with HIV-1 (PLWH) under combined antiretroviral therapy (cART). Previous studies demonstrated that the frequency of HIV-1-specific CD8+ T cells is reduced under cART and their functional ability remains impaired. These studies analyzed T-cell responses to a small number of HIV-1 epitopes or overlapping HIV-1 peptides. Therefore, the features of CD8+ T cells specific for HIV-1 epitopes under cART remain only partially clarified. Here, we analyzed CD8+ T cells specific for 63 well-characterized epitopes in 90 PLWH. We demonstrated that CD8+ T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and that long-term cART enhanced or restored the ability of HIV-1-specific T cells to proliferate in vitro. This study implies that some HIV-1-specific T cells would be useful as effector cells for curative treatment.

Keywords: AIDS; CD8+ T cells; HIV-1; cART; epitope.

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD8-Positive T-Lymphocytes* / cytology
  • CD8-Positive T-Lymphocytes* / drug effects
  • CD8-Positive T-Lymphocytes* / immunology
  • Epitopes, T-Lymphocyte* / drug effects
  • Epitopes, T-Lymphocyte* / immunology
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / therapy
  • HIV-1* / drug effects
  • HIV-1* / immunology
  • Humans

Substances

  • Anti-HIV Agents
  • Epitopes, T-Lymphocyte